Details
Stereochemistry | ACHIRAL |
Molecular Formula | C25H26N7O8P |
Molecular Weight | 583.4898 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
COC1=CN=C(N2C=NC(C)=N2)C3=C1C(=CN3COP(O)(O)=O)C(=O)C(=O)N4CCN(CC4)C(=O)C5=CC=CC=C5
InChI
InChIKey=SWMDAPWAQQTBOG-UHFFFAOYSA-N
InChI=1S/C25H26N7O8P/c1-16-27-14-32(28-16)23-21-20(19(39-2)12-26-23)18(13-31(21)15-40-41(36,37)38)22(33)25(35)30-10-8-29(9-11-30)24(34)17-6-4-3-5-7-17/h3-7,12-14H,8-11,15H2,1-2H3,(H2,36,37,38)
DescriptionSources: https://aidsinfo.nih.gov/drugs/508/fostemsavir/0/patient | https://www.hiv.uw.edu/page/treatment/drugs/fostemsavir | https://www.ncbi.nlm.nih.gov/pubmed/27922453https://www.ncbi.nlm.nih.gov/pubmed/25401969Curator's Comment: Description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/22547625
https://www.ncbi.nlm.nih.gov/pubmed/23774428
Sources: https://aidsinfo.nih.gov/drugs/508/fostemsavir/0/patient | https://www.hiv.uw.edu/page/treatment/drugs/fostemsavir | https://www.ncbi.nlm.nih.gov/pubmed/27922453https://www.ncbi.nlm.nih.gov/pubmed/25401969
Curator's Comment: Description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/22547625
https://www.ncbi.nlm.nih.gov/pubmed/23774428
Temsavir (BMS-626529) is an attachment inhibitor (AI) in clinical development (administered as prodrug BMS-663068) that binds to HIV-1 gp120. Temsavir displays in vitro activity against HIV-1 envelopes with C-C chemokine receptor type 5 (CCR5-), C-X-C chemokine receptor type 4 (CXCR4), and dual tropism. It also is active against almost all HIV-1 subtypes tested except for subtype CRF01-AE and possibly group O. Temsavir can inhibit both CD4-induced and CD4-independent formation of the "open state" four-stranded gp120 bridging sheet, and the subsequent formation and exposure of the chemokine co-receptor binding site. This unique mechanism of action prevents the initial interaction of HIV-1 with the host CD4+ T cell, and subsequent HIV-1 binding and entry. Temsavir is administered as a phosphonooxymethyl ester prodrug (BMS-663068), which was developed to improve the solubility and dissolution of Temsavir. Temsavir is currently being investigated clinically through the use of the prodrug BMS-663068, and a Phase III study of BMS-663068 in HIV-1-infected treatment-experienced subjects is ongoing (NCT02362503).
Originator
Sources: http://adisinsight.springer.com/drugs/800031504
Curator's Comment: # Bristol-Myers Squibb
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL378 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22547625 |
|||
Target ID: CHEMBL378 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22547625 |
2.26 nM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | Unknown Approved UseUnknown |
|||
Primary | Unknown Approved UseUnknown |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
1770 ng/mL |
600 mg 2 times / day multiple, oral dose: 600 mg route of administration: Oral experiment type: MULTIPLE co-administered: other antiretroviral drugs |
TEMSAVIR plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
3.39 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22896665/ |
1200 mg 2 times / day multiple, oral dose: 1200 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
TEMSAVIR plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: FED |
|
2.55 ug/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01009814 |
1200 mg single, oral dose: 1200 mg route of administration: oral experiment type: single co-administered: |
TEMSAVIR plasma | Homo sapiens |
|
3.18 ug/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01009814 |
1200 mg 1 times / 12 hours multiple, oral dose: 1200 mg route of administration: oral experiment type: multiple co-administered: |
TEMSAVIR plasma | Homo sapiens |
|
3.38999999999999 ug/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01009814 |
1200 mg 1 times / 12 hours multiple, oral dose: 1200 mg route of administration: oral experiment type: multiple co-administered: |
TEMSAVIR plasma | Homo sapiens |
|
3.61 ug/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01009814 |
1200 mg 1 times / 12 hours multiple, oral dose: 1200 mg route of administration: oral experiment type: multiple co-administered: |
TEMSAVIR plasma | Homo sapiens |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
12900 ng × h/mL |
600 mg 2 times / day multiple, oral dose: 600 mg route of administration: Oral experiment type: MULTIPLE co-administered: other antiretroviral drugs |
TEMSAVIR plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
42.6 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22896665/ |
1200 mg 2 times / day multiple, oral dose: 1200 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
TEMSAVIR plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: FED |
|
13.8 ug*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01009814 |
1200 mg single, oral dose: 1200 mg route of administration: oral experiment type: single co-administered: |
TEMSAVIR plasma | Homo sapiens |
|
19.5 ug*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01009814 |
1200 mg 1 times / 12 hours multiple, oral dose: 1200 mg route of administration: oral experiment type: multiple co-administered: |
TEMSAVIR plasma | Homo sapiens |
|
22.5 ug*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01009814 |
1200 mg 1 times / 12 hours multiple, oral dose: 1200 mg route of administration: oral experiment type: multiple co-administered: |
TEMSAVIR plasma | Homo sapiens |
|
42.6 ug*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01009814 |
1200 mg 1 times / 12 hours multiple, oral dose: 1200 mg route of administration: oral experiment type: multiple co-administered: |
TEMSAVIR plasma | Homo sapiens |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
11 h |
600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered: |
TEMSAVIR plasma | Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
Funbound
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
26.9% |
600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered: |
TEMSAVIR plasma | Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
Doses
Dose | Population | Adverse events |
---|---|---|
600 mg 2 times / day steady, oral Recommended Dose: 600 mg, 2 times / day Route: oral Route: steady Dose: 600 mg, 2 times / day Co-administed with:: optimized background therapy Sources: |
unhealthy, 17-43 years n = 271 Health Status: unhealthy Condition: HIV-1 infection Age Group: 17-43 years Sex: M+F Population Size: 271 Sources: |
Disc. AE: Immune reconstitution inflammatory syndrome... Other AEs: Nausea, Diarrhea... AEs leading to discontinuation/dose reduction: Immune reconstitution inflammatory syndrome (grade 3, 3%) Other AEs:Nausea (grade 1-4, 10%) Sources: Diarrhea (grade 1-4, 4%) Headache (grade 1-4, 4%) Abdominal pain (grade 1-4, 3%) Dyspepsia (grade 1-4, 3%) Fatigue (grade 1-4, 3%) Rash (grade 1-4, 3%) Sleep disturbance (grade 1-4, 3%) Immune reconstitution inflammatory syndrome (grade 1-4, 2%) Somnolence (grade 1-4, 2%) Vomiting (grade 1-4, 2%) ALT increased (grade 3-4, 5%) AST increased (grade 3-4, 4%) Direct bilirubin increased (grade 3, 7%) Bilirubin increased (grade 3-4, 3%) Creatinine increased (grade 3-4, 19%) Creatine kinase increased (grade 3-4, 2%) Hemoglobin decreased (grade 3-4, 6%) Hyperglycemia (grade 3-4, 4%) Lipase increased (grade 3-4, 5%) Neutrophils reduced (grade 3-4, 4%) Blood triglycerides increased (grade 3-4, 5%) |
600 mg 2 times / day steady, oral Recommended Dose: 600 mg, 2 times / day Route: oral Route: steady Dose: 600 mg, 2 times / day Co-administed with:: ritonavir(100 mg; oral; 1/day) Sources: |
healthy, 18-49 years n = 18 Health Status: healthy Age Group: 18-49 years Sex: M+F Population Size: 18 Sources: |
Other AEs: Scleral icterus, Abdominal pain... Other AEs: Scleral icterus (5.6%) Sources: Abdominal pain (5.6%) Nausea (5.6%) |
600 mg 2 times / day steady, oral Recommended Dose: 600 mg, 2 times / day Route: oral Route: steady Dose: 600 mg, 2 times / day Co-administed with:: atazanavir(300 mg; oral; 1/day) Sources: ritonavir(100 mg; oral; 1/day) |
healthy, 18-49 years n = 36 Health Status: healthy Age Group: 18-49 years Sex: M+F Population Size: 36 Sources: |
Other AEs: Scleral icterus, Abdominal pain... Other AEs: Scleral icterus (27.8%) Sources: Abdominal pain (11.1%) Headache (13.9%) Dizziness (5.6%) Nausea (8.3%) Musculoskeletal chest pain (2.8%) |
600 mg 2 times / day steady, oral Recommended Dose: 600 mg, 2 times / day Route: oral Route: steady Dose: 600 mg, 2 times / day Sources: |
healthy, 18-49 years n = 36 Health Status: healthy Age Group: 18-49 years Sex: M+F Population Size: 36 Sources: |
Other AEs: Headache... |
1050 mg 2 times / day steady, oral (mean) Studied dose Dose: 1050 mg, 2 times / day Route: oral Route: steady Dose: 1050 mg, 2 times / day Co-administed with:: raltegravir and tenofovir disoproxil fumarate Sources: |
unhealthy, adults n = 200 Health Status: unhealthy Condition: HIV-1 infection Age Group: adults Sex: M+F Population Size: 200 Sources: |
Other AEs: Headache... |
1200 mg 1 times / day steady, oral Studied dose Dose: 1200 mg, 1 times / day Route: oral Route: steady Dose: 1200 mg, 1 times / day Co-administed with:: raltegravir and tenofovir disoproxil fumarate Sources: |
unhealthy, adults n = 50 Health Status: unhealthy Condition: HIV-1 infection Age Group: adults Sex: M+F Population Size: 50 Sources: |
Disc. AE: Disseminated tuberculosis, Back pain... AEs leading to discontinuation/dose reduction: Disseminated tuberculosis (2%) Sources: Back pain (2%) |
400 mg 2 times / day steady, oral Studied dose Dose: 400 mg, 2 times / day Route: oral Route: steady Dose: 400 mg, 2 times / day Co-administed with:: raltegravir and tenofovir disoproxil fumarate Sources: |
unhealthy, adults n = 50 Health Status: unhealthy Condition: HIV-1 infection Age Group: adults Sex: M+F Population Size: 50 Sources: |
Disc. AE: Ischaemia... AEs leading to discontinuation/dose reduction: Ischaemia (2%) Sources: |
800 mg 2 times / day steady, oral Studied dose Dose: 800 mg, 2 times / day Route: oral Route: steady Dose: 800 mg, 2 times / day Co-administed with:: raltegravir and tenofovir disoproxil fumarate Sources: |
unhealthy, adults n = 49 Health Status: unhealthy Condition: HIV-1 infection Age Group: adults Sex: M+F Population Size: 49 Sources: |
Disc. AE: Bone tuberculosis, Acute renal failure... AEs leading to discontinuation/dose reduction: Bone tuberculosis (2%) Sources: Acute renal failure (2%) |
2400 mg 2 times / day steady, oral Highest studied dose Dose: 2400 mg, 2 times / day Route: oral Route: steady Dose: 2400 mg, 2 times / day Sources: |
healthy n = 15 |
Other AEs: QT interval prolonged... |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Nausea | grade 1-4, 10% | 600 mg 2 times / day steady, oral Recommended Dose: 600 mg, 2 times / day Route: oral Route: steady Dose: 600 mg, 2 times / day Co-administed with:: optimized background therapy Sources: |
unhealthy, 17-43 years n = 271 Health Status: unhealthy Condition: HIV-1 infection Age Group: 17-43 years Sex: M+F Population Size: 271 Sources: |
Immune reconstitution inflammatory syndrome | grade 1-4, 2% | 600 mg 2 times / day steady, oral Recommended Dose: 600 mg, 2 times / day Route: oral Route: steady Dose: 600 mg, 2 times / day Co-administed with:: optimized background therapy Sources: |
unhealthy, 17-43 years n = 271 Health Status: unhealthy Condition: HIV-1 infection Age Group: 17-43 years Sex: M+F Population Size: 271 Sources: |
Somnolence | grade 1-4, 2% | 600 mg 2 times / day steady, oral Recommended Dose: 600 mg, 2 times / day Route: oral Route: steady Dose: 600 mg, 2 times / day Co-administed with:: optimized background therapy Sources: |
unhealthy, 17-43 years n = 271 Health Status: unhealthy Condition: HIV-1 infection Age Group: 17-43 years Sex: M+F Population Size: 271 Sources: |
Vomiting | grade 1-4, 2% | 600 mg 2 times / day steady, oral Recommended Dose: 600 mg, 2 times / day Route: oral Route: steady Dose: 600 mg, 2 times / day Co-administed with:: optimized background therapy Sources: |
unhealthy, 17-43 years n = 271 Health Status: unhealthy Condition: HIV-1 infection Age Group: 17-43 years Sex: M+F Population Size: 271 Sources: |
Abdominal pain | grade 1-4, 3% | 600 mg 2 times / day steady, oral Recommended Dose: 600 mg, 2 times / day Route: oral Route: steady Dose: 600 mg, 2 times / day Co-administed with:: optimized background therapy Sources: |
unhealthy, 17-43 years n = 271 Health Status: unhealthy Condition: HIV-1 infection Age Group: 17-43 years Sex: M+F Population Size: 271 Sources: |
Dyspepsia | grade 1-4, 3% | 600 mg 2 times / day steady, oral Recommended Dose: 600 mg, 2 times / day Route: oral Route: steady Dose: 600 mg, 2 times / day Co-administed with:: optimized background therapy Sources: |
unhealthy, 17-43 years n = 271 Health Status: unhealthy Condition: HIV-1 infection Age Group: 17-43 years Sex: M+F Population Size: 271 Sources: |
Fatigue | grade 1-4, 3% | 600 mg 2 times / day steady, oral Recommended Dose: 600 mg, 2 times / day Route: oral Route: steady Dose: 600 mg, 2 times / day Co-administed with:: optimized background therapy Sources: |
unhealthy, 17-43 years n = 271 Health Status: unhealthy Condition: HIV-1 infection Age Group: 17-43 years Sex: M+F Population Size: 271 Sources: |
Rash | grade 1-4, 3% | 600 mg 2 times / day steady, oral Recommended Dose: 600 mg, 2 times / day Route: oral Route: steady Dose: 600 mg, 2 times / day Co-administed with:: optimized background therapy Sources: |
unhealthy, 17-43 years n = 271 Health Status: unhealthy Condition: HIV-1 infection Age Group: 17-43 years Sex: M+F Population Size: 271 Sources: |
Sleep disturbance | grade 1-4, 3% | 600 mg 2 times / day steady, oral Recommended Dose: 600 mg, 2 times / day Route: oral Route: steady Dose: 600 mg, 2 times / day Co-administed with:: optimized background therapy Sources: |
unhealthy, 17-43 years n = 271 Health Status: unhealthy Condition: HIV-1 infection Age Group: 17-43 years Sex: M+F Population Size: 271 Sources: |
Diarrhea | grade 1-4, 4% | 600 mg 2 times / day steady, oral Recommended Dose: 600 mg, 2 times / day Route: oral Route: steady Dose: 600 mg, 2 times / day Co-administed with:: optimized background therapy Sources: |
unhealthy, 17-43 years n = 271 Health Status: unhealthy Condition: HIV-1 infection Age Group: 17-43 years Sex: M+F Population Size: 271 Sources: |
Headache | grade 1-4, 4% | 600 mg 2 times / day steady, oral Recommended Dose: 600 mg, 2 times / day Route: oral Route: steady Dose: 600 mg, 2 times / day Co-administed with:: optimized background therapy Sources: |
unhealthy, 17-43 years n = 271 Health Status: unhealthy Condition: HIV-1 infection Age Group: 17-43 years Sex: M+F Population Size: 271 Sources: |
Immune reconstitution inflammatory syndrome | grade 3, 3% Disc. AE |
600 mg 2 times / day steady, oral Recommended Dose: 600 mg, 2 times / day Route: oral Route: steady Dose: 600 mg, 2 times / day Co-administed with:: optimized background therapy Sources: |
unhealthy, 17-43 years n = 271 Health Status: unhealthy Condition: HIV-1 infection Age Group: 17-43 years Sex: M+F Population Size: 271 Sources: |
Direct bilirubin increased | grade 3, 7% | 600 mg 2 times / day steady, oral Recommended Dose: 600 mg, 2 times / day Route: oral Route: steady Dose: 600 mg, 2 times / day Co-administed with:: optimized background therapy Sources: |
unhealthy, 17-43 years n = 271 Health Status: unhealthy Condition: HIV-1 infection Age Group: 17-43 years Sex: M+F Population Size: 271 Sources: |
Creatinine increased | grade 3-4, 19% | 600 mg 2 times / day steady, oral Recommended Dose: 600 mg, 2 times / day Route: oral Route: steady Dose: 600 mg, 2 times / day Co-administed with:: optimized background therapy Sources: |
unhealthy, 17-43 years n = 271 Health Status: unhealthy Condition: HIV-1 infection Age Group: 17-43 years Sex: M+F Population Size: 271 Sources: |
Creatine kinase increased | grade 3-4, 2% | 600 mg 2 times / day steady, oral Recommended Dose: 600 mg, 2 times / day Route: oral Route: steady Dose: 600 mg, 2 times / day Co-administed with:: optimized background therapy Sources: |
unhealthy, 17-43 years n = 271 Health Status: unhealthy Condition: HIV-1 infection Age Group: 17-43 years Sex: M+F Population Size: 271 Sources: |
Bilirubin increased | grade 3-4, 3% | 600 mg 2 times / day steady, oral Recommended Dose: 600 mg, 2 times / day Route: oral Route: steady Dose: 600 mg, 2 times / day Co-administed with:: optimized background therapy Sources: |
unhealthy, 17-43 years n = 271 Health Status: unhealthy Condition: HIV-1 infection Age Group: 17-43 years Sex: M+F Population Size: 271 Sources: |
AST increased | grade 3-4, 4% | 600 mg 2 times / day steady, oral Recommended Dose: 600 mg, 2 times / day Route: oral Route: steady Dose: 600 mg, 2 times / day Co-administed with:: optimized background therapy Sources: |
unhealthy, 17-43 years n = 271 Health Status: unhealthy Condition: HIV-1 infection Age Group: 17-43 years Sex: M+F Population Size: 271 Sources: |
Hyperglycemia | grade 3-4, 4% | 600 mg 2 times / day steady, oral Recommended Dose: 600 mg, 2 times / day Route: oral Route: steady Dose: 600 mg, 2 times / day Co-administed with:: optimized background therapy Sources: |
unhealthy, 17-43 years n = 271 Health Status: unhealthy Condition: HIV-1 infection Age Group: 17-43 years Sex: M+F Population Size: 271 Sources: |
Neutrophils reduced | grade 3-4, 4% | 600 mg 2 times / day steady, oral Recommended Dose: 600 mg, 2 times / day Route: oral Route: steady Dose: 600 mg, 2 times / day Co-administed with:: optimized background therapy Sources: |
unhealthy, 17-43 years n = 271 Health Status: unhealthy Condition: HIV-1 infection Age Group: 17-43 years Sex: M+F Population Size: 271 Sources: |
ALT increased | grade 3-4, 5% | 600 mg 2 times / day steady, oral Recommended Dose: 600 mg, 2 times / day Route: oral Route: steady Dose: 600 mg, 2 times / day Co-administed with:: optimized background therapy Sources: |
unhealthy, 17-43 years n = 271 Health Status: unhealthy Condition: HIV-1 infection Age Group: 17-43 years Sex: M+F Population Size: 271 Sources: |
Blood triglycerides increased | grade 3-4, 5% | 600 mg 2 times / day steady, oral Recommended Dose: 600 mg, 2 times / day Route: oral Route: steady Dose: 600 mg, 2 times / day Co-administed with:: optimized background therapy Sources: |
unhealthy, 17-43 years n = 271 Health Status: unhealthy Condition: HIV-1 infection Age Group: 17-43 years Sex: M+F Population Size: 271 Sources: |
Lipase increased | grade 3-4, 5% | 600 mg 2 times / day steady, oral Recommended Dose: 600 mg, 2 times / day Route: oral Route: steady Dose: 600 mg, 2 times / day Co-administed with:: optimized background therapy Sources: |
unhealthy, 17-43 years n = 271 Health Status: unhealthy Condition: HIV-1 infection Age Group: 17-43 years Sex: M+F Population Size: 271 Sources: |
Hemoglobin decreased | grade 3-4, 6% | 600 mg 2 times / day steady, oral Recommended Dose: 600 mg, 2 times / day Route: oral Route: steady Dose: 600 mg, 2 times / day Co-administed with:: optimized background therapy Sources: |
unhealthy, 17-43 years n = 271 Health Status: unhealthy Condition: HIV-1 infection Age Group: 17-43 years Sex: M+F Population Size: 271 Sources: |
Abdominal pain | 5.6% | 600 mg 2 times / day steady, oral Recommended Dose: 600 mg, 2 times / day Route: oral Route: steady Dose: 600 mg, 2 times / day Co-administed with:: ritonavir(100 mg; oral; 1/day) Sources: |
healthy, 18-49 years n = 18 Health Status: healthy Age Group: 18-49 years Sex: M+F Population Size: 18 Sources: |
Nausea | 5.6% | 600 mg 2 times / day steady, oral Recommended Dose: 600 mg, 2 times / day Route: oral Route: steady Dose: 600 mg, 2 times / day Co-administed with:: ritonavir(100 mg; oral; 1/day) Sources: |
healthy, 18-49 years n = 18 Health Status: healthy Age Group: 18-49 years Sex: M+F Population Size: 18 Sources: |
Scleral icterus | 5.6% | 600 mg 2 times / day steady, oral Recommended Dose: 600 mg, 2 times / day Route: oral Route: steady Dose: 600 mg, 2 times / day Co-administed with:: ritonavir(100 mg; oral; 1/day) Sources: |
healthy, 18-49 years n = 18 Health Status: healthy Age Group: 18-49 years Sex: M+F Population Size: 18 Sources: |
Abdominal pain | 11.1% | 600 mg 2 times / day steady, oral Recommended Dose: 600 mg, 2 times / day Route: oral Route: steady Dose: 600 mg, 2 times / day Co-administed with:: atazanavir(300 mg; oral; 1/day) Sources: ritonavir(100 mg; oral; 1/day) |
healthy, 18-49 years n = 36 Health Status: healthy Age Group: 18-49 years Sex: M+F Population Size: 36 Sources: |
Headache | 13.9% | 600 mg 2 times / day steady, oral Recommended Dose: 600 mg, 2 times / day Route: oral Route: steady Dose: 600 mg, 2 times / day Co-administed with:: atazanavir(300 mg; oral; 1/day) Sources: ritonavir(100 mg; oral; 1/day) |
healthy, 18-49 years n = 36 Health Status: healthy Age Group: 18-49 years Sex: M+F Population Size: 36 Sources: |
Musculoskeletal chest pain | 2.8% | 600 mg 2 times / day steady, oral Recommended Dose: 600 mg, 2 times / day Route: oral Route: steady Dose: 600 mg, 2 times / day Co-administed with:: atazanavir(300 mg; oral; 1/day) Sources: ritonavir(100 mg; oral; 1/day) |
healthy, 18-49 years n = 36 Health Status: healthy Age Group: 18-49 years Sex: M+F Population Size: 36 Sources: |
Scleral icterus | 27.8% | 600 mg 2 times / day steady, oral Recommended Dose: 600 mg, 2 times / day Route: oral Route: steady Dose: 600 mg, 2 times / day Co-administed with:: atazanavir(300 mg; oral; 1/day) Sources: ritonavir(100 mg; oral; 1/day) |
healthy, 18-49 years n = 36 Health Status: healthy Age Group: 18-49 years Sex: M+F Population Size: 36 Sources: |
Dizziness | 5.6% | 600 mg 2 times / day steady, oral Recommended Dose: 600 mg, 2 times / day Route: oral Route: steady Dose: 600 mg, 2 times / day Co-administed with:: atazanavir(300 mg; oral; 1/day) Sources: ritonavir(100 mg; oral; 1/day) |
healthy, 18-49 years n = 36 Health Status: healthy Age Group: 18-49 years Sex: M+F Population Size: 36 Sources: |
Nausea | 8.3% | 600 mg 2 times / day steady, oral Recommended Dose: 600 mg, 2 times / day Route: oral Route: steady Dose: 600 mg, 2 times / day Co-administed with:: atazanavir(300 mg; oral; 1/day) Sources: ritonavir(100 mg; oral; 1/day) |
healthy, 18-49 years n = 36 Health Status: healthy Age Group: 18-49 years Sex: M+F Population Size: 36 Sources: |
Headache | 5.6% | 600 mg 2 times / day steady, oral Recommended Dose: 600 mg, 2 times / day Route: oral Route: steady Dose: 600 mg, 2 times / day Sources: |
healthy, 18-49 years n = 36 Health Status: healthy Age Group: 18-49 years Sex: M+F Population Size: 36 Sources: |
Headache | grade 1, 14% | 1050 mg 2 times / day steady, oral (mean) Studied dose Dose: 1050 mg, 2 times / day Route: oral Route: steady Dose: 1050 mg, 2 times / day Co-administed with:: raltegravir and tenofovir disoproxil fumarate Sources: |
unhealthy, adults n = 200 Health Status: unhealthy Condition: HIV-1 infection Age Group: adults Sex: M+F Population Size: 200 Sources: |
Back pain | 2% Disc. AE |
1200 mg 1 times / day steady, oral Studied dose Dose: 1200 mg, 1 times / day Route: oral Route: steady Dose: 1200 mg, 1 times / day Co-administed with:: raltegravir and tenofovir disoproxil fumarate Sources: |
unhealthy, adults n = 50 Health Status: unhealthy Condition: HIV-1 infection Age Group: adults Sex: M+F Population Size: 50 Sources: |
Disseminated tuberculosis | 2% Disc. AE |
1200 mg 1 times / day steady, oral Studied dose Dose: 1200 mg, 1 times / day Route: oral Route: steady Dose: 1200 mg, 1 times / day Co-administed with:: raltegravir and tenofovir disoproxil fumarate Sources: |
unhealthy, adults n = 50 Health Status: unhealthy Condition: HIV-1 infection Age Group: adults Sex: M+F Population Size: 50 Sources: |
Ischaemia | 2% Disc. AE |
400 mg 2 times / day steady, oral Studied dose Dose: 400 mg, 2 times / day Route: oral Route: steady Dose: 400 mg, 2 times / day Co-administed with:: raltegravir and tenofovir disoproxil fumarate Sources: |
unhealthy, adults n = 50 Health Status: unhealthy Condition: HIV-1 infection Age Group: adults Sex: M+F Population Size: 50 Sources: |
Acute renal failure | 2% Disc. AE |
800 mg 2 times / day steady, oral Studied dose Dose: 800 mg, 2 times / day Route: oral Route: steady Dose: 800 mg, 2 times / day Co-administed with:: raltegravir and tenofovir disoproxil fumarate Sources: |
unhealthy, adults n = 49 Health Status: unhealthy Condition: HIV-1 infection Age Group: adults Sex: M+F Population Size: 49 Sources: |
Bone tuberculosis | 2% Disc. AE |
800 mg 2 times / day steady, oral Studied dose Dose: 800 mg, 2 times / day Route: oral Route: steady Dose: 800 mg, 2 times / day Co-administed with:: raltegravir and tenofovir disoproxil fumarate Sources: |
unhealthy, adults n = 49 Health Status: unhealthy Condition: HIV-1 infection Age Group: adults Sex: M+F Population Size: 49 Sources: |
QT interval prolonged | 2400 mg 2 times / day steady, oral Highest studied dose Dose: 2400 mg, 2 times / day Route: oral Route: steady Dose: 2400 mg, 2 times / day Sources: |
healthy n = 15 |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
---|---|---|
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Page: 182.0 |
no [IC50 110 uM] | |||
Page: 184.0 |
no [IC50 32.8 uM] | |||
Page: 176.0 |
no [IC50 >10 uM] | |||
Page: 176.0 |
no [IC50 >10 uM] | |||
Page: 177.0 |
no [IC50 >10 uM] | |||
Page: 177.0 |
no [IC50 >10 uM] | |||
Page: 184.0 |
no [IC50 >100 uM] | |||
Page: 176.0 |
no [IC50 >100 uM] | |||
Page: 176.0 |
no [IC50 >100 uM] | |||
Page: 176.0 |
no [IC50 >100 uM] | |||
Page: 176.0 |
no [IC50 >100 uM] | |||
Page: 176.0 |
no [IC50 >100 uM] | |||
Page: 176.0 |
no [IC50 >100 uM] | |||
Page: 181.0 |
no [IC50 >250 uM] | |||
Page: 181.0 |
no [IC50 >250 uM] | |||
Page: 174.0 |
no [IC50 >40 uM] | |||
Page: 175.0 |
no [IC50 >40 uM] | |||
Page: 174.0 |
no [IC50 >40 uM] | |||
Page: 175.0 |
no [IC50 >40 uM] | |||
Page: 174.0 |
no [IC50 >40 uM] | |||
Page: 174.0 |
no [IC50 >40 uM] | |||
Page: 175.0 |
no [IC50 >40 uM] | |||
Page: 175.0 |
no [IC50 >40 uM] | |||
Page: 184.0 |
no [IC50 >50 uM] | |||
Page: 183.0 |
no [IC50 >50 uM] | |||
Page: 183.0 |
no [IC50 >50 uM] | |||
Page: 182.0 |
no [IC50 >50 uM] | |||
Page: 181.0 |
no [Inhibition 25 uM] | |||
Page: 36.0 |
no | |||
Page: 177.0 |
no | |||
Page: 178.0 |
no | |||
Page: 178.0 |
no | |||
Page: 36.0 |
no | |||
Page: 36, 183 |
yes [IC50 12.2 uM] | |||
Page: 182.0 |
yes [IC50 18.5 uM] | |||
Page: 36, 114 |
yes | |||
Page: 36, 114, 180 |
yes | |||
Page: 36, 114, 181 |
yes |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Page: 35.0 |
minor | |||
Page: 173.0 |
no | |||
Page: 173.0 |
no | |||
Page: 173.0 |
no | |||
Page: 173.0 |
no | |||
Page: 173.0 |
no | |||
Page: 173.0 |
no | |||
Page: 173.0 |
no | |||
Page: 173.0 |
no | |||
Page: 173.0 |
no | |||
Page: 173.0 |
no | |||
Page: 173.0 |
no | |||
Page: 173.0 |
no | |||
Page: 173.0 |
no | |||
Page: 35, 179 |
yes | |||
Page: 35, 179 |
yes | |||
Page: 35.0 |
yes | |||
Page: 35, 111, 112, 113 |
yes | yes (co-administration study) Comment: coadministration of fostemsavir with rifampin significantly decreases temsavir plasma concentrations, reduced temsavir AUC by 80%; coadministration of fostemsavir with drugs that are strong CYP3A inducers result in decreased concentrations of temsavir. Page: 35, 111, 112, 113 |
Tox targets
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Page: 69.0 |
PubMed
Title | Date | PubMed |
---|---|---|
In vitro antiviral characteristics of HIV-1 attachment inhibitor BMS-626529, the active component of the prodrug BMS-663068. | 2012 Jul |
|
Safety and efficacy of the HIV-1 attachment inhibitor prodrug BMS-663068 in treatment-experienced individuals: 24 week results of AI438011, a phase 2b, randomised controlled trial. | 2015 Oct |
|
Model-Based Phase 3 Dose Selection for HIV-1 Attachment Inhibitor Prodrug BMS-663068 in HIV-1-Infected Patients: Population Pharmacokinetics/Pharmacodynamics of the Active Moiety, BMS-626529. | 2016 May |
|
Safety and efficacy of the HIV-1 attachment inhibitor prodrug fostemsavir in antiretroviral-experienced subjects: week 48 analysis of AI438011, a Phase IIb, randomized controlled trial. | 2017 |
|
[What can new substances offer?]. | 2017 Jun |
|
Current Status of the Pharmacokinetics and Pharmacodynamics of HIV-1 Entry Inhibitors and HIV Therapy. | 2017 Oct 16 |
Sample Use Guides
A phase 2b trial enrolled treatment-experienced adults with HIV infection and randomized study subjects to one of four doses of fostemsavir (400 mg twice daily, 800 mg twice daily, 600 mg once daily, or 1200 mg once daily).
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/22547625
Curator's Comment: Temsavir (BMS-626529) had half-maximal effective concentration (EC(50)) values of <10 nM against the vast majority of HIV-1 viral isolates; however, susceptibility varied by >6 log(10), with half-maximal effective concentration values in the low pM range against the most susceptible viruses.
BMS-626529 (an active moiety of BMS-663068) exhibits an average EC50 against LAI of 0.7 +/-0.4 nM.
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AB-45
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ACTIVE MOIETY
SALT/SOLVATE (PARENT)
SALT/SOLVATE (PARENT)
SALT/SOLVATE (PARENT)
SUBSTANCE RECORD